Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome

Abstract

Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel coronavirus, but its immunopathological mechanisms have not yet been fully elucidated. We investigated changes in plasma T helper (Th) cell cytokines, inflammatory cytokines and chemokines in 20 patients diagnosed with SARS. Cytokine profile of SARS patients showed marked elevation of Th1 cytokine interferon (IFN)-gamma, inflammatory cytokines interleukin (IL)-1, IL-6 and IL-12 for at least 2 weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumour necrosis factor (TNF)-alpha, anti-inflammatory cytokine IL-10, Th1 cytokine IL-2 and Th2 cytokine IL-4. The chemokine profile demonstrated significant elevation of neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-gamma-inducible protein-10 (IP-10). Corticosteroid reduced significantly IL-8, MCP-1 and IP-10 concentrations from 5 to 8 days after treatment (all P < 0.001). Together, the elevation of Th1 cytokine IFN-gamma, inflammatory cytokines IL-1, IL-6 and IL-12 and chemokines IL-8, MCP-1 and IP-10 confirmed the activation of Th1 cell-mediated immunity and hyperinnate inflammatory response in SARS through the accumulation of monocytes/macrophages and neutrophils.

Fig. 1

Box & whiskers plots of changes in plasma cytokine concentrations following day of disease onset in the 20 SARS patients. Normal ranges: (a) IL-1β < 3·9 ng/l; (b) IL-6 < 3·1 ng/l; (c) IL-10 < 7·8 ng/l; (d) IL-12 < 7·8 ng/l; (e) TNF-α < 10·0 ng/l; and (f) IFN-γ < 15·6 ng/l. *Significantly elevated compared to normal values (all P < 0·05).

Fig. 1

Box & whiskers plots of changes in plasma cytokine concentrations following day of disease onset in the 20 SARS patients. Normal ranges: (a) IL-1β < 3·9 ng/l; (b) IL-6 < 3·1 ng/l; (c) IL-10 < 7·8 ng/l; (d) IL-12 < 7·8 ng/l; (e) TNF-α < 10·0 ng/l; and (f) IFN-γ < 15·6 ng/l. *Significantly elevated compared to normal values (all P < 0·05).

Fig. 2

Box & whiskers plots of changes in plasma chemokine concentrations following day of disease onset in the 20 SARS patients. Normal ranges: (a) IL-8 < 5·0 ng/l; (b) IP-10 202–1480 ng/l; (c) MCP-1 < 10–57 ng/l; (d) MIG 48–482 ng/l; and (e) RANTES 4382–18783 ng/l. *Significantly elevated compared to normal values (all P < 0·05).

Fig. 2

Box & whiskers plots of changes in plasma chemokine concentrations following day of disease onset in the 20 SARS patients. Normal ranges: (a) IL-8 < 5·0 ng/l; (b) IP-10 202–1480 ng/l; (c) MCP-1 < 10–57 ng/l; (d) MIG 48–482 ng/l; and (e) RANTES 4382–18783 ng/l. *Significantly elevated compared to normal values (all P < 0·05).

Fig. 3

Box & whiskers plots of changes in plasma cytokine and chemokine concentrations following day of disease onset in SARS patients (a) treated (n = 13) and (b) not treated (n = 7) with pulsed methylprednisolone. Although not reaching statistical significance, median concentrations in (a) are higher than corresponding values in (b).